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NPC1L1 and SR-BI are Involved in Intestinal Cholesterol Absorption from Small-Size Lipid Donors

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Lipids

Abstract

In the human intestinal content after a meal, cholesterol is dispersed in a complex mixture of emulsified droplets, vesicles, mixed micelles and precipitated material. The aim of this study was to determine the contribution of the main intestinal cholesterol transporters (NPC1L1, SR-BI) to the absorption processes, using different cholesterol-solubilizing donors. Cholesterol donors prepared with different taurocholate concentrations were added to an apical medium of differentiated TC7/Caco-2 cells. As the taurocholate concentrations increased, cholesterol donor size decreased (from 712 to 7 nm in diameter), which enhanced cholesterol absorption in a dose-dependent manner (38-fold). Two transport processes were observed: (1) absorption from large donors exhibited low-capacity transport with no noticeable transporter contribution; (2) efficient cholesterol absorption occurs from small lipid donors (≤23 nm diameter), mainly due to NPC1L1 and SR-BI involvement. In addition, bile acids significantly increased mRNA and protein expression of NPC1L1, but not of SR-BI. In conclusion, bile acids present in the intestinal lumen and the micelles enhance intestinal cholesterol transport into the cell by two different regulatory processes: by reducing the lipid donor size, so that small-size mixed micelles can more easily access brush-border membrane transporters, and by increasing the expression level of the enterocyte NPC1L1. These mechanisms could account for the important inter-individual variations observed in cholesterol intestinal absorption.

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Abbreviations

BA:

Bile acids

CL:

Cholesterol

DCA:

Deoxycholic acid

DMEM:

Dulbecco’s modified Eagle’s medium

NPC1L1:

Niemann–Pick C1-like 1

SR-BI:

Scavenger receptor class B type I

TCA:

Taurocholic acid

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Acknowledgments

We thank G. Diraison and Malvern Instruments (Vénissieux, France) for technical assistance. We thank L. Cara for his helpful comments about the preparation of the experiment.

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Authors and Affiliations

  1. INRA, UMR1260 «Nutriments Lipidiques et Prévention des Maladies Métaboliques», INSERM, U476, Univ Aix-Marseille 1, Univ Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, 27 bld Jean Moulin, 13385, Marseille, France

    Ziad Haikal, Barbara Play, Jean-François Landrier, Annie Giraud, Odette Ghiringhelli, Denis Lairon & Dominique Jourdheuil-Rahmani

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  1. Ziad Haikal
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  2. Barbara Play
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  3. Jean-François Landrier
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  4. Annie Giraud
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  5. Odette Ghiringhelli
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  6. Denis Lairon
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  7. Dominique Jourdheuil-Rahmani
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Corresponding author

Correspondence to Dominique Jourdheuil-Rahmani.

Additional information

This work was supported by grants from the Nouvelle Société Française d’Athérosclérose and from the Comité Nutrition et Santé, Institut Appert, France.

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Haikal, Z., Play, B., Landrier, JF. et al. NPC1L1 and SR-BI are Involved in Intestinal Cholesterol Absorption from Small-Size Lipid Donors. Lipids 43, 401–408 (2008). https://doi.org/10.1007/s11745-008-3172-7

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  • DOI: https://doi.org/10.1007/s11745-008-3172-7

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